Abstract

Objective: Bipolar disorder (BD) is emerging as an illness marred by neurocognitive deficits, many of which do not resolve on recovery. Deficits affecting working memory (WM) in particular appear to be significant. WM comprises temporally separated biological processes that involve the on-line retention and manipulation of information. Previous neuroimaging studies have not sought to dissect the individual contributions of WM and examined WM subprocesses in euthymic BD. In this study, we investigated the encode, delay and response components of WM to identify the neural substrates and respective contributions to the WM deficits found in BD.Methods: We used event-related functional magnetic resonance imaging and a parametric WM task, incorporating 3 load conditions, to delineate individual WM subprocesses in 10 euthymic BD patients and 10 control subjects.Results: Patients exhibited attenuated patterns of activity, predominantly in frontal brain regions, across all WM components.Conclusions: Based on the attenuated activity observed in the patients, the clinical deficits in WM found in BD may reflect broad fronto-cortico-limbic dysfunction that is not confined to any single WM component. This is important in understanding the pathophysiology of BD and for future studies on executive functions in patients with this illness.

Acknowledgements: Thanks to Dr. Adrian M. Owen for his comments on this paper. Thanks to the Australian Rotary Health Research Fund, the National Health and Medical Research Council for financial support, and the National Institute of Schizophrenia and Allied Disorders for infrastructure support.

Contributors: Drs Lagopoulos and Malhi designed the study. Dr. Lagopoulos and Ms. Ivanovski aquired the data, and all the authors analyzed it. All authors contributed to the writing and revision of the article. All authors gave final approval for the article to be published.